We are investigating the mechanism of hemoglobin degradation in erythroid cells. The systems under study are K562 cells, reticulocytes, and red cells infected with malarial parasites. We plan to identify degradative products as well as any critical proteinases or cofactors, and gain some understanding of the molecular mechanism of protein degradation in normal and diseased cells. Our data suggests that the acid proteolytic activity previously observed in extracts of the mouse malarial parasite P. berghei is actually of red cell origin. A parasitic activity is revealed, however, upon activation with dithiothreitol and is apparently responsible for hemozoin production. A corresponding proteinase has also been identified and partially purified from the human malarial parasite P. falciparum. In studies of the K562 human erythroleukemic cell line, we have found that uninduced and hemin-induced cells have similar levels of a cathepsin D enzyme.